Physiologic variation in rate of urine flow in mammals is ascribed principally to reabsorption from distal tubules and collecting ducts of a varying quantity of nearly solute-free water (1-4). Water reabsorption is brought about by bulk flow or diffusion (5-8) incited by the difference in osmotic pressure between the luminal contents and the hypertonic fluid of the adjacent renal medullary interstitium, a process promoted by the action of endogenous vasopressin upon the permeability of the intervening membranes (7, 9). Elaboration of urine much less than maximally dilute increases the osmolality of luminal fluid as it progresses down the most distal portion of the nephron; the result must be to raise the diffusion pressure of all substances dissolved in luminal fluid.Two highly diffusible substances, the gases NH3 and CO2, are present in solution in luminal fluid together with their hydrated forms NH4OH and H2CO3, in turn in equilibrium, so as to constitute two buffer systems, with the ionized species NH4+ and HCO3-, respectively. If, as a result of the reabsorption of solute-free water, these gases are reabsorbed by diffusion, the existence and magnitude of the process should be reflected in alterations in the acid-base composition of voided urine no less than by changes in the rate of excretion of total ammonia and total carbon 1962-63. dioxide. Examination of the effects of water diuresis in normal man upon these various parameters has provided indirect evidence that the gases NH3 and CO2 do in fact diffuse out of the nephron's lumen during antidiuresis (10-12).1 This communication presents evidence that the rate of urinary ammonia excretion is largely determined by factors affecting the net diffusion of the free base NH3 into the distal portion of the nephron; the evidence further indicates that some NH3, having diffused into the lumen, subsequently diffuses back into the renal interstitium as a result of reabsorption of water from the lumen. METHODSExperimental design. Subjects were 12 healthy adult male volunteers whose rate of urinary flow was caused to vary between 1 ml per minute and the physiologic ceiling by controlled water-drinking. Serial, timed urine collections were made at intervals of about 12 minutes by voluntary emptying of the bladder. The individual experiments, generally comprising 20 or more collections, were begun about 8 a.m. in subjects who fasted overnight and remained upright during and for at least an hour before the experiment. When alkaline or mark-1 "Ammonia" means total ammonia. NH, includes NH4OH when ratios of the buffer species are in question, and HCO3 includes anhydrous CO, in the analagous context. NH4, is not considered a form of buffered H' except that "total H`" excretion includes NH,+.It has been inferred from experiments on toad bladder and other membranes (5) that vasopressin promotes osmotic movement of water out of the nephron by hydraulic flow through pores rather than by diffusion. The facts about the toad bladder are disputed (8), and there is no direct info...

We studied the long-term effects of membrane-active antiarrhythmic agents on chronic ventricular arrhythmias in patients who have survived prehospital cardiac arrest. Among 16 patients treated with a dose-adjusted, plasma level-monitored antiarrhythmic regimen, eight have survived for longer than 12 months and eight have had recurrent cardiac arrests (RCAs). Monthly Holter monitor tapes (HM) recorded during the 4 months before the eight RCAs were compared with monthly HM tapes matched for time of entry and duration of follow-up in the eight patients who did not have RCAs. Transient or persistent complex ventricular ectopic depolarizations (VEDs) have been recorded on 47 of the 63 monthly HM tapes (75%). The difference between VEDs in the RCA patients (mean 153 VEDs/hr, median 19 VEDs/hr) and VEDs in the patients who have not had RCA (mean 122 VEDs/hr, median 8 VEDs/hr) was not significant (p less than 0.2); nor was there a predictable relationship between therapeutic plasma levels of antiarrhythmic agents and the frequency and complexity of chronic asymptomatic VEDs (therapeutic levels--mean 104 VEDs/hr, median 6 VEDs/hr; subtherapeutic levels--mean 184 VEDs/hr, median 21 VEDs/hr). Differences were not significant (p greater than 0.1). In contrast, all eight RCA patients had unstable plasma levels (21 of 31 determinations subtherapeutic) while six of the eight patients who have not had RCA had consistently therapeutic levels (p less than 0.01). Thus, adequate plasma levels of antiarrhythmic agents may protect against RCA, despite failure to suppress VEDs predictably. The apparent dissociation between predictable suppression of chronic VEDs and protection against RCA suggests that clinical effectiveness of these agents may not be best measured by their effect on chronic VEDs.

Fifty patients who received a new hypocholesterolemic agent, probucol, in a dosage of 0.5 gm twice daily, were studied for one year. Mean pretreatment serum cholesterol and triglyceride values were 329 mg/100 ml and 360 mg/100 ml respectively. Baseline lipoprotein electrophoreses showed 17 Fredrickson phenotypic patterns of type 2, 6 of type 3, 10 of type 4, 3 of type 5, and 14 non‐definitive patterns. After twelve months of treatment with probucol, the mean serum cholesterol level was 263 mg/100 ml (a minus 20 per cent change) and the mean triglyceride level was 293 mg/100 ml (a minus 19 per cent change) for all patients. The median baseline cholesterol level was 311 mg/100 ml and the median cholesterol value during twelve months of therapy was 252 mg/100 ml, a reduction of 19 per cent. The median baseline triglyceride level was 174 mg/100 ml and the median triglyceride value during twelve months of therapy was 147 mg/100 ml, a reduction of 16 per cent. Significant changes were noted in the serum lipoprotein patterns; the majority of type 2 and type 3 changed to the non‐definitive pattern, but the majority of type 4 and type 5 remained unchanged. Seven patients had xanthelasmas, but all these lesions decreased in size and 3 lesions disappeared during probucol therapy. Side effects were minimal. About a third of the patients had mild transient flatulence or slight transient eosinophilia. There was no effect on prothrombin time. Probucol appears to be a safe and effective hypolipidemic agent. It can also induce changes in serum lipoprotein patterns and markedly reduce the size of xanthelasmas.

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The prevalence of pets in households of patients with rheumatoid arthritis (RA) is compared to arthritic (non‐RA) and nonarthritic control patients in this epidemiologic survey. During the 5‐year period prior to diseaseonset RA patients had greater exposure to dogs, cats, or birds (combined), dogs, and sick animals than control patients. This finding raises the possibility that pets might serve as a reservoir for an infectious agent(s) capable of initiating RA.